Agnes Ginges Laboratory for Diseases of the Aorta

Cardiovascular disease is a major cause of morbidity and mortality worldwide. Many cardiovascular diseases, such as atherosclerosis, are largely caused by the dysfunctional regulation of smooth muscle cells, the principle cell type found in blood vessel walls. We have identified a new stem cell mediated pathway in the regulation of smooth muscle cells. Identifying effectors that target this new pathway has clear implications to treat cardiovascular diseases and will lead to the development of novel therapeutics.

The Aorta Lab is currently investigating the following projects:

Understanding cellular stemness and their role in cardiovascular diseases

Cardiovascular disease is a major cause of morbidity and mortality worldwide. Many cardiovascular diseases, such as atherosclerosis, are largely caused by the dysfunctional regulation of smooth muscle cells, the principle cell type found in blood vessel walls. We have identified a new stem cell mediated pathway in the regulation of smooth muscle cells. Identifying effectors that target this new pathway has clear implications to treat cardiovascular diseases and will lead to the development of novel therapeutics.

Epigenetic regulation of miRNAs in cardiovascular diseases

Many major human cardiovascular diseases are caused by the uncontrolled proliferation and differentiation of smooth muscle cells, the main cell type in blood vessel walls. The mechanisms that regulate this reversible differentiation remain unclear. Our data suggests that changes in smooth muscle cells are controlled by TET2-dependent miRNAs. Understanding this novel pathway has the potential to reverse some of the unwanted pathological changes associated with aberrant smooth muscle function.

Identification of a novel biomarker for the earlier detection of cardiovascular events

Cardiovascular disease is the leading cause of mortality worldwide and affects over 3.7 million Australians. Early detection of affected individuals is often challenging as symptoms occur later in the disease and are often only detected once the disease has become established. This makes treatment more complex and often requires invasive surgery which itself is associated with disability and death. The cornerstone of cardiovascular disease prevention is in the early identification of at-risk individuals, however current biomarkers only have modest predictive value. We have discovered a novel biomarker that can be used as a prognostic biomarker for the earlier detection and diagnosis of at-risk individuals.

Deciphering the role of a novel gene in protecting against aortic aneurysms (in collaboration with Prof. Jennifer Gamble)

Aortic aneurysm is a pathological condition characterised by weakening of the vessel wall that eventually leads to rupture and death. It is the 13th leading cause of death worldwide and is an increasing source of disability and mortality in Australia. Despite its frequent occurrence in the population (affecting approximately 1 in 500 individuals), it is a significantly understudied disease where the causes of aneurysm formation and progression are unknown. Currently, high-risk surgical procedures remain the only treatment option for patients. We have recently identified a novel gene that has now been shown to be criticial for inhibiting aneurysm formation, and ongoing studies will determine how this gene functions to prevent aneurysms and whether manipulation of this gene can reverse or halt aneurysmal development and progression.

Recent Novel Prize winning work demonstrating the ability to turn adult cells to stem cells has opened up exciting avenues for disease modelling. This is particularly true for the study of diseases where tissue samples are near-impossible to obtain for research. Utilising this technique, we will derive patient-specific stem cells to study complex diseases in the cardiovascular system. These resultant cell lines will represent a unique cellular source for modelling complex diseases that can faithfully capture the human disease and provide the first steps to improved understanding of the cause of many disease and its potential treatments.

Dr Renjing Liu

Phone: (02) 9565 2667Email: r.liu@centenary.org.au

Dr Liu received her PhD from the University of Sydney in 2010. Dr. Liu was awarded the international Sir Keith Murdoch Fellowshipin 2010 to train at the Yale Stem Cell Centre with one of the pioneers in induced pluripotent stem cells and the epigenetics field. Dr. Liu then received the prestigious Yale Browne-Cox Fellowship and was recruited to complete a second postdoctoral traineeship at the Yale Cardiovascular Research Centre. This Centre is often regarded as one of the best cardiovascular research institutes in America. Dr. Liu returned to Australia in late 2013 and was awarded the Inaugural David Richmond Fellowship to head the newly established Aorta Lab at the Centenary Institute. Since her return, Dr. Liu was awarded the University of Sydney Early Career Fellowship, and award given to top new investigators with projects that have the most potential and significant outcomes. Recently, Dr. Liu was also awarded the prestigious Ramaciotti Biomedical Award for her work on finding a novel biomarker for the early detection of cardiovascular diseases.